The therapy and diagnosis of diseases at the cellular and molecular levels will be improved greatly with the development of medical imaging technologies that can not only monitor the delivery of analytical probes or therapeutic agents but also enable comprehensive and objective evaluation of treatment effects. As an emerging noninvasive, nonionizing light-based technology presenting both high contrast and high spatial resolution, photoacoustic tomography (PAT) may be developed into a novel and promising molecular imaging modality which will generate innovations and play a critical role in medicine. We propose to investigate an even more advanced spectroscopic PAT (SPAT) technique using inflammatory arthritic disease models, patterned after widely known, very costly, painful, and disabling disorders, for demonstration of the method. SPAT, when aided by a newly developed gold nanocolloid contrast agent, may create innovations with an extensive impact in various biomedical applications, not only in more efficient evaluation of drug effects in living laboratory animals but also in optimized therapeutic decisions in clinical practice. The SPAT system for human/animal inflammatory arthritis will be developed on a stand-alone commercial ultrasound unit which, in an exclusive research mode allows acquisition of light-induced ultrasound signals with 64 independent channels simultaneously. This capability will for the first time enable near real-time 2D PAT and fast speed 3D PAT. Gold nanorods with the optical absorption peak tuned to the NIR region will be conjugated with Etanercept (Enbrel(r)), an FDA approved drug for rheumatoid arthritis. Due to the strong optical absorption by gold nanorods, the SPAT system working with a designed PVDF array transducer holds promise in imaging the drug uptake in regional arthritic tissues. Besides drug delivery monitoring, the unique ability of SPAT in evaluating treatment efficacy will also be examined through the comparison with nuclear imaging and MRI conducted on the same animals quasi-simultaneously. By imaging the morphological and physiological hallmarks of synovitis including hypervascularization and hypoxia, SPAT may realize comprehensive evaluation of the early responses of arthritic tissues to the pharmaceutical treatment. This research is anticipated to develop instrumentation and techniques that may significantly contribute to diagnostic imaging and therapeutic monitoring of various disorders including inflammatory diseases and cancer.